Optimal dose of meropenem for the treatment of neonatal sepsis: Dosing guideline variations and clinical practice deviations

Authors

Muhammad Ahmer Raza, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Bu-Fan Yao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Hai-Yan Shi, Department of Clinical Pharmacy, Clinical Trial Center, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.
Hai-Yan Xu, Department of Neonatology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
Guo-Xiang Hao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
John Van Den Anker, Division of Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA.
Wei Zhao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Document Type

Journal Article

Publication Date

3-12-2022

Journal

British journal of clinical pharmacology

DOI

10.1111/bcp.15308

Keywords

clinical practice; guidelines; meropenem; neonates

Abstract

AIMS: Meropenem is increasingly used to treat neonatal sepsis. There are several guidelines recommending different dosing regimens of meropenem in neonates. Furthermore, deviations from these guidelines regularly occur in daily clinical practice. Therefore, the current study aimed to evaluate the variations of meropenem dosing guidelines and compare the difference between guideline and clinical practice in terms of the probability of target attainment. METHODS: This study is based on a population pharmacokinetic model. After defining the predictive performance of the model, Monte Carlo simulations were used to calculate the probability of target attainment of the currently existing dosing guidelines of meropenem and their use in daily clinical practice. RESULTS: Two guidelines and two labels were included in the Monte Carlo simulations. For 70% fT (fraction of time when the free meropenem concentration exceeded the minimum inhibitory concentration during the dosing interval), the probability of target attainment of four recommended doses ranged from 59% to 88% (MIC = 2 mg·L ) and from 17% to 47% (MIC = 8 mg·L ). At the clinical practice evaluation, only 20% of patients attained target exposure for the MIC of 8 mg·L with 70% fT , which was much less than those found in the Food and Drug Administration labels (40%). CONCLUSION: This model-based population pharmacokinetics simulation showed that improper guidelines and/or clinical practice deviations will result in low probability of target attainment for patients infected with resistant bacteria and critically ill patients. It is important to develop and adhere to evidence-based and clinically pragmatic guidelines.

APA Citation

Raza, Muhammad Ahmer; Yao, Bu-Fan; Shi, Hai-Yan; Xu, Hai-Yan; Hao, Guo-Xiang; Van Den Anker, John; and Zhao, Wei, "Optimal dose of meropenem for the treatment of neonatal sepsis: Dosing guideline variations and clinical practice deviations" (2022). GW Authored Works. Paper 599.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/599

Department

Pediatrics